Non-invasive Ultrasound Elasticity Imaging (UEI) in Crohn's Disease While current imaging systems such as computed tomography (CT) scanning can identify inflammation in Crohn's disease, there are no imaging tools to identify which patients have significant intestinal fibrosis. Healing between flares of inflammation allows the intestine to reconstitute its epithelium, but this healing process results in the deposition of fibrotic scar tissue. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine, requiring surgery in 20% of patients within 3 years of diagnosis, and in 57% of patients after 10 years of disease. This has a substantial impact on quality of life and medical costs. When Crohn's patients have abdominal pain and vomiting, this indicates severe narrowing of the small intestine. This can be due to inflammation, which can be treated with medical therapy, or due to chronic fibrosis, which requires surgery. Patients are treated empirically with steroids with their many side effects. Many patients would be better treated with surgery if we could identify which patients truly have severe intestinal fibrosis causing their intestinal strictures. Local ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and timely management of intestinal fibrosis in Crohn's disease. This method allows complete characterization of the altered local tissue elastic properties and local intestine mechanics. Furthermore, it does so with high spatial resolution, offering excellent sensitivity, specificity, accuracy and precision. The mechanical properties of the intestine are estimated directly from intramural strain rather than inferred from intestine thickness and/or diameter changes. The direct nature of the measurement procedure is ideal for local assessment of tissue mechanical changes that occur with the development of fibrosis in the course of inflammatory bowel disease. If our hypotheses are correct, this method can be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained with commercially available scanners. The fundamental hypotheses of this proposal are: 1.UEI can measure local changes in the elastic properties of the intestinal wall associated with the progression of fibrosis. 2. Local mechanical changes of the intestine wall as measured by UEI can predict the severity and extent of local fibrosis of the intestine resulting from previous inflammation. 3. UEI with speckle tracking can be used to non-invasively measure highly localized intestinal compliance changes in rodents, and is readily translatable into a clinical diagnostic tool in humans. A wide range of technical and scientific issues must be investigated to fully exploit the capabilities of the techniques proposed. Therefore, the two specific aims of this application are: 1. to determine whether noninvasive UEI can distinguish between the mechanical properties of fibrotic colon and normal colon in rats treated chronically with TNBS (trinitrobenzenesulfonic acid) enemas;and 2. To determine whether UEI is able to detect and measure the severity and extent of fibrosis in patients with Crohn's disease. PUBLIC HEALTH RELEVANCE: Repeated cycles of inflammation often lead to clinically significant fibrosis and stenosis of the intestine, requiring surgery in 20% of patients within 3 years of diagnosis, and in 57% of patients after 10 years of disease. This has a substantial impact on quality of life and medical costs. When Crohn's patients have abdominal pain and vomiting, this indicates severe narrowing of the small intestine. This can be due to inflammation, which can be treated with medical therapy, or due to chronic fibrosis, which requires surgery. Patients are treated empirically with steroids with their many side effects. Many patients would be better treated with surgery if we could identify which patients truly have severe intestinal fibrosis causing their intestinal strictures. While current imaging systems such as computed tomography (CT) scanning can identify inflammation in Crohn's disease, there are no imaging tools to identify which patients have significant intestinal fibrosis. The proposed local ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and timely management of intestinal fibrosis in Crohn's disease. This method allows complete characterization of the altered local tissue elastic properties and local intestine mechanics. This method also can be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained with commercially available scanners.